EPA Registration Division contact: Andrew Ertman (703) 308

- 9367

Interregional Research Project Number 4 (IR

- 4)

PP #2E8107

EPA has received a pesticide petition ( 2E8107 ) from IR

- 4 Project, 500 College Road East, Suite 201W, Princeton, NJ 08540, proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180, by establishing a tolerance for residues of the insecticide fenpropathrin, alpha

- cyano

- 3

- phenoxybenzyl 2,2,3,3

- tetrameth ylcyclopropanecarboxylate in or on the follow ing commodities and crop group s : Barley, grain at 0.04 parts per million (ppm); Barley, hay at 3.0 parts per million (ppm); Barley, straw at 2.0 parts per million (ppm) ; Vegetable, fruiting, g roup 8

- 10 at 1.0 p arts per million (ppm) ; Fru it, citrus, g roup 10

- 10 at 2.0 parts per million (ppm) ; Fruit, pome, g roup 11

- 10 at 5.0 parts per million ; Bushberry s ubgroup 13

- 07B at 3.0 parts per million (ppm) ; Fruit, vine cli mbing, except fuzzy kiwifruit, s ubgroup 13

- 07F at 5.0 parts per million (ppm) ; and Berry, low growing, s ubgroup 13

- 07G at 2.0 parts per million (ppm)

. IR

- 4 also proposes, upon approval of the aforementioned tolerances, to remove established tolerances for residues of the insecticide fenpropathrin, al pha

- cyano

- 3

- phenoxybenzyl 2,2,3,3

- tetramethylcyclopropanecarboxylate in or on the following commodit ies and crop groups: Vegetable, fruiting, Group 8; Fruit, citrus, group 10; Fruit, pome, group 11; Bushberry subgroup 13B; Juneberry; Salal; Grape; and Stra wberry. E PA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted d a ta at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.2

A. Residue Chemistry

1. Plant metabolism

. The plant metabolism of fenpropathrin has been studied in five different crop plant species: Cotton, apple, to mato, cabbage, and bean. Each of the studies involved foliar treatment of the plants under either greenhouse or field conditions. In all studies the total toxic residue is best defined as parent, fenpropathrin. The primary metabolic pathway for fenpropathr in in plants is similar to that in mammals. There are no qualitatively unique plant metabolites.

2. Analytical method. Adequate analytical methodology is available to detect and quantify fenpropathrin at residue levels in numerous matrices. The methods use solvent extraction and partition and/or column chromatography clean

- up steps, followed by separation and quantitation using capillary gas liquid chromatography (GLC) with FID. The extraction efficiency has been validated using radiocarbon samples from the plant and animal metabolism studies. The enforcement methods have been validated at independent laboratories and by EPA. The limit of quantification (LOQ) for fenpropathrin in raw agricultural commodity samples is usually 0.01 ppm.

3. Magnitude of r esidues

. Residue data has been submitted for Barley and the requested tolerances are adequately supported.

B. Toxicological Profile

Additional toxicological studies have been completed and have been submitted to reduce the uncertainty factor associated w ith fenpropathrin.

1. Acute toxicity. An assessment of the toxic effects caused by fenpropathrin is discussed in III. A. and III. B. of the Federal Register dated September 23, 2005 (OPP

2005

- 0133) (FRL

- 7738

- 7).

2. Genotoxicty. An assessment of the toxic effects caused by fenpropathrin is discussed in III. A. and III. B. of the Federal Register dated September 23, 2005 (OPP

2005

- 0133) (FRL

- 7738

- 7).

3. Reproductive and developmental toxicity. An assessment of the toxic effects caused by fenpropathrin is discussed in III. A. and III. B. of the Federal Register dated September 23, 2005 (OPP

- 2005

- 0133) (FRL

- 7738

- 7).

4. Subchronic toxicity. An assessment of the toxic effects caused by fenpropat hrin is discussed in III. A. and III. B. of the Federal Register dated September 23, 2005 (OPP

2005

- 0133) (FRL

- 7738

- 7).

5. Chronic toxicity. An assessment of the toxic effects caused by fenpropathrin is discussed in III. A. and III. B. of the Federal R egister dated September 23, 2005 (OPP

2005

- 0133) (FRL

- 7738

- 7).3

6. Animal metabolism

. Four metabolites were found in the urine of rats dosed with alcohol labeled fenpropathrin. The major metabolites were the sulfate conjugate of 3

- (4'

- hydroxyphenoxy)ben zoic acid and 3

- phenoxybenzoic acid (22

- 44% and 3

- 9% of the administered dose, respectively). The major urinary metabolites of the acid

- labeled fenpropathrin were TMPA

- glucuronic acid and TMPA

- CH2OH (11

- 26% and 6

- 10% of the administered dose, respectively) . None of the parent chemical was found in urine.

The major elimination products in the feces included the parent chemical (13

- 34% of the administered dose) and four metabolites. The fecal metabolites (percentage of administered dose) included CH2OH

- fenpr opathrin (9

- 20%), 4'

- OH

- fenpropathrin (4

- 11%), COOH

- fenpropathrin (2

- 7%), and 4'

- OH

- CH2OH

- fenpropathrin (2

- 7%). There are no qualitatively unique plant metabolites. The primary aglycones are identical in both plants and animals; the only difference is in t he nature of the conjugating moieties employed.

7. Metabolite toxicology

. The metabolism and potential toxicity of the small amounts of terminal plant metabolites have been tested on mammals. Glucoside conjugates of 3

- phenoxy

- benzyl alcohol and 3

- phenoxy benzoic acid, administered orally to rats, were absorbed as the corresponding aglycones following cleavage of the glycoside linkage in the gut. Normal metabolic pathways rapidly and completely eliminated the free or reconjugated aglycones. The glucose conj ugates of 3

- phenoxybenzyl alcohol and 3

- phenoxy

- benzoic acid are less toxic to mice than the corresponding aglycones.

8. Endocrine disruption

. No special studies to investigate the potential for estrogenic or other endocrine effects of fenpropathrin have been performed. However, as referenced above (see toxicological profile), a large and detailed toxicology database exists for the compound including studies acceptable to the Agency in all required categories. These studies include evaluations of reproduc tion and reproductive toxicity and detailed pathology and histology of endocrine organs following repeated or long

term exposure. These studies are considered capable of revealing endocrine effects and no such effects were observed.

C. Aggregate Exposure

1. Dietary exposure

. Chronic and acute dietary exposure analyses were performed for fenpropathrin using anticipated residues, and accounting for proportion of the crop treated. The crops included in the analyses are the raw agricultural commodities
cotto nseed, currants, peanuts, strawberries, soybeans, lingonberry, juneberry, salal, and grapes, and the crop groupings succulent shelled pea (6B), head and stem brassica (5A), fruiting vegetables (8), cucurbit vegetables (9), citrus fruits (10), bushberry (13 B) and pome fruits (11); processed products from these crops; and the resulting secondary residues in meat, milk, and eggs. Soybeans (and soybean products) were entered into the analyses using tolerance

- level residues and 1% of the crop treated for chronic assessments, and 2% of the crop treated for acute assessments. Proportion of crop treated was assumed to be equal for all crops in a crop grouping.4

Based on the minimal dietary intake of olives and caneberries, the magnitude of uses currently registered , and current aPAD and cPAD levels, it is not necessary to complete an additional dietary analysis to include these uses. Also, additional toxicological studies have been completed and will be submitted to reduce the uncertainty factor associated with fen propathrin. None of the studies lowered the endpoints utilized in the risk
assessment.

i. Food

. a. Acute. Acute dietary exposure was calculated for the U.S. population, females (13+), males (20+ years) and five children subgroups. At the 99.9th percenti le of exposure, the acute population adjusted dose (aPAD) of 0.06 milligrams/kilogram body weight/day (mg/kg bwt/day) is not exceeded.

b. Chronic. Chronic dietary exposure was calculated for the U.S. population and 25 population subgroups. Chronic dietary exposure was at or below 0.6% of the chronic population adjusted dose (cPAD) of 0.025 mg/kg bwt/day, with apples being the commodity contributing the most to chronic exposure. Generally speaking, the Agency has no cause for concern if total residue contribution for published and proposed tolerances is less than 100% of the cPAD.

ii. Drinking water. Since fenpropathrin is applied outdoors to growing agricultural crops, the potential exists for fenpropathrin to reach ground water or surface water that may be used for drinking water. To further quantify exposure from drinking water, potential surface water and ground water concentrations for fenpropathrin were estimated using First Index Reservoir Screening Tool (FIRST) and Screening Concentration in Groundwater (SCI

- GROW) modeling. Use on citrus, the most intense field use, was modeled. SCI

- GROW modeling indicated that fenpropathrin would not be detected in ground water. FIRST modeling of potentia l surface water concentrations of fenpropathrin yielded annual average parts per billion (0.833 ppb) and peak day (1.030 ppb) concentrations. These estimated drinking water environmental concentrations (DWEC) could be used for chronic and acute exposures, respectively.

2. Non

- dietary exposure

. No endpoints of concern were identified by the Health Effects Division, Hazard Identification Assessment Review Committee for dermal or inhalation exposures of any duration. Thus, no risk assessment is needed.

D. C umulative Effects

EPA issued a Pyrethroid Cumulative Risk Assessment on October 4, 2011. The Assessment incorporates multiple high

- end inputs and combines the highest exposures/risk estimates across all pathways in a deterministic fashion resulting in a screening level assessment which is highly conservative and health protective. This cumulative assessment considered all registered uses of pyrethrins/pyrethroids and5

included exposure from food, drinking water and residential settings from the oral

, dermal and inhalation routes of exposure. This screening level assessment supports the conclusion that cumulative estimated risks from existing pyrethrins/pyrethroid uses are not of concern. Further, there is sufficient room in the pyrethroid cumulativ e risk cup to support consideration of new pyrethroids (i.e., currently unregistered pyrethroid pesticides) and new uses of existing pyrethroids having similar toxicity profiles and use patterns to those in the Assessment.

E. Safety Determination

1. U. S. population. i. Acute. The potential acute exposure from food to the U.S. population and various non

- child/infant population subgroups provide values well below the aPAD . In a conservative policy, the Agency has no cause for concern if total acute exposure calculated for the 99.9th percentile is less than 100% of the aPAD. Acute DWLOC values are not exceeded by modeled DWEC values. It can be concluded that there is a rea sonable certainty that no harm will result to the overall U.S. population and
many non

- child/infant subgroups from aggregate, acute exposure to fenpropathrin residues.

ii. Chronic. Using the dietary exposure assessment procedures, the calculated chron ic dietary exposure resulting from residue exposure from existing and proposed uses of fenpropathrin is minimal. The estimated chronic dietary exposure from food for the overall U.S. population and many non

- child/infant subgroups ranges from 0.6% (children 1

- 6 years old, 0.000155 mg/kg bwt/day) to 0.1% (several groups) of the cPAD. Generally, the Agency has no cause for concern if total residue contribution is less than 100% of the cPAD. Chronic drinking water levels of concern (DWLOC) values are not exceed ed by modeled drinking water estimated concentration (DWEC) values. It can be concluded that there is a reasonable certainty that no harm will result to the overall U.S. population and many non

- child/infant subgroups from aggregate, chronic dietary
exposur e to fenpropathrin residues.

2. Infants and children

. The estimated chronic dietary exposure from food to infant and child subgroups ranges from 0.6% children 1

- 6 years old, 0.000155 mg/kg bwt/day to 0.1% nursing infants, 0.000026 mg/kg bwt/day of the cP AD. Generally, the Agency has no cause for concern if total residue contribution is less than 100% of the cPAD. Chronic DWLOC values are not exceeded by modeled DWEC values. It can be concluded that there is a reasonable certainty that no harm will result to infant and child subgroups of the U.S. population from aggregate, chronic exposure to fenpropathrin residues.6

F. International Tolerances

The following are the existing Codex MRLs for Fenpropathrin:

There are small differences between the Section 408 tolerances and the Codex MRL values for secondary residues in animal products. These minor differences are mainly caused by differences in the methods used to calculate animal feed dietary exposure. The only substantial difference between the U S tolerance and the Codex MRL value is for tomatoes. The JMPR reviewer required that the MRL exceed the highest field residue value rounded up to unit value. The EPA reviewer agreed with Valent that one set of field residue samples was possibly compromised by the presence of a high rate processing treatment nearby. High outliers were ignored, and the tolerance was set at 0.6 ppm.